| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
|
Purity: ≥98%
Vatalanib (PTK787 or ZK-222584, cpg-79787 2HCl) 2HCl is a novel, potent and orally bioavailable inhibitor of VEGFR2/KDR with potential anticancer activity. In a cell-free experiment, it inhibits VEGFR2/KDR with an IC50 of 37 nM, is less effective against VEGFR1/Flt-1, and is 18-fold more potent against VEGFR3/Flt-4. With strong anti-proliferative activity in vitro and strong antitumor efficaciousness in vivo, it is an anilinophthalazine analog. The protein kinase domains of VEGFR 1 and 2 are bound by vatalanib, which then inhibits them. The PDGF receptor, c-Kit, and c-Fms are among the related receptor tyrosine kinases that this agent binds to and inhibits.
| Targets |
VEGFR2/KDR (IC50 = 37 nM); VEGFR1/FLT1 (IC50 = 77 nM); VEGFR2/Flk1 (IC50 = 270 nM); PDGFRβ (IC50 = 580 nM); VEGFR3/FLT4 (IC50 = 660 μM)
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay |
In vitro kinase assays employ recombinant GST-fused kinase domains that are expressed in baculovirus and purified over glutathione-Sepharose. They are carried out as filter binding assays in 96-well plates. γ-[33P]ATP The phosphate donor in this scenario is ATP, while the acceptor is poly-(Glu:Tyr 4:1) peptide. Recombinant GST-fusion proteins are diluted, based on their specific activity, in 20 mM Tris·HCl (pH 7.5) containing 1-3 mM MnCl2, 3-10 mM MgCl2, 0.25 mg/mL polyethylene glycol 20000, and 1 mM DTT. The optimized buffer conditions for each GST-fused kinase include 20 mM Tris-HCl buffer (pH 7.5), 1-3 mM MnCl2, 3-10 mM MgCl2, 3-6 μg/mL poly-(Glu:Tyr 4:1), 0.25 mg/mL polyethylene glycol 20000, 8 μM ATP, 10 μM sodium vanadate, 1 mM DTT, and 0.2 μCi[γ-33P]ATP in a total volume of 30 μL, with or without a test substance. The incubation period lasts for 10 minutes at room temperature. Addition of 10 μL of 250 mM EDTA stops the reaction. The volume is divided in half (20 μL) and placed onto an Immobilon-polyvinylidene difluoride membrane using a 96-well filter system. After a thorough washing in 0.5% H3PO4, the membrane is submerged in ethanol. Following drying, the addition of Microscint cocktail and scintillation counting are carried out. In these as well as all the assays listed below, the IC50s for PTK787/ZK 222584 or SU5416 are determined using linear regression analysis of the percentage inhibition.
|
|
| Cell Assay |
An endothelial cell proliferation test based on BrdUrd incorporation is used to determine whether PTK787/ZK 222584 can inhibit a functional response to VEGF. Subconfluent HUVECs are seeded into 96-well plates that have been coated with 1.5% gelatin, and the plates are then incubated in growth medium at 37 °C with 5% CO2. The growth medium is changed after a day to basal medium that contains 1.5% FCS and a consistent amount of either VEGF (50 ng/mL), bFGF (0.5 ng/mL), or FCS (5%), with or without PTK787/ZK 222584. There are also wells without a growth factor included as a control. Prior to fixation, blocking, and the addition of peroxidase-labeled anti-BrdUrd antibody, cells are incubated for a further 24 hours after the addition of BrdUrd labeling solution. Using 3,3′5,5′-tetramethylbenzidine substrate, bound antibody is then identified. This reaction product is colored and can be measured spectrophotometrically at 450 nm.
|
|
| Animal Protocol |
The dorsal flank of C57/C6 mice is implanted subcutaneously with a porous Teflon chamber (volume: 0.5 mL) containing 0.8% w/v agar containing heparin (20 units/mL) with or without growth factor (3 μg/mL human VEGF, 2 μg/mL human PDGF). One day prior to chamber implantation and for five days following, the mice are given either vehicle (water) or Vatalanib (12.5, 25 or 50 mg/kg dihydrochloride p.o. once daily). The mice are put to death and the chambers are taken out at the conclusion of the treatment. The vascularized tissue encircling the chamber is carefully removed, weighed, and its hemoglobin content is measured to determine the amount of blood present.
|
|
| References | ||
| Additional Infomation |
Vatalanib dihydrochloride is a member of phthalazines.
|
| Molecular Formula |
C20H15CLN4.2HCL
|
|
|---|---|---|
| Molecular Weight |
419.73
|
|
| Exact Mass |
382.075
|
|
| Elemental Analysis |
C, 57.23; H, 4.08; Cl, 25.34; N, 13.35
|
|
| CAS # |
212141-51-0
|
|
| Related CAS # |
Vatalanib;212141-54-3;Vatalanib succinate;212142-18-2
|
|
| PubChem CID |
22386467
|
|
| Appearance |
White to off-white crystalline solid
|
|
| Boiling Point |
587.8ºC at760mmHg
|
|
| Melting Point |
268-2700ºC
|
|
| Flash Point |
309.3ºC
|
|
| Vapour Pressure |
7.94E-16mmHg at 25°C
|
|
| LogP |
6.689
|
|
| Hydrogen Bond Donor Count |
3
|
|
| Hydrogen Bond Acceptor Count |
4
|
|
| Rotatable Bond Count |
4
|
|
| Heavy Atom Count |
27
|
|
| Complexity |
407
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])N([H])C1C2=C([H])C([H])=C([H])C([H])=C2C(C([H])([H])C2C([H])=C([H])N=C([H])C=2[H])=NN=1.Cl[H].Cl[H]
|
|
| InChi Key |
AZUQEHCMDUSRLH-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C20H15ClN4.2ClH/c21-15-5-7-16(8-6-15)23-20-18-4-2-1-3-17(18)19(24-25-20)13-14-9-11-22-12-10-14;;/h1-12H,13H2,(H,23,25);2*1H
|
|
| Chemical Name |
N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine;dihydrochloride
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.96 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.96 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3825 mL | 11.9124 mL | 23.8248 mL | |
| 5 mM | 0.4765 mL | 2.3825 mL | 4.7650 mL | |
| 10 mM | 0.2382 mL | 1.1912 mL | 2.3825 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00268918 | Completed | Drug: Docetaxel Drug: PTK787 |
Ovarian Cancer Endometrial Cancer |
Dana-Farber Cancer Institute | September 2005 | Phase 1 |
| NCT00117299 | Completed | Drug: PTK787/ZK222584 | Sarcoma | University of Helsinki | September 2004 | Phase 2 |
| NCT00056459 | Completed | Drug: Vatalanib | Colorectal Neoplasms Colonic Neoplasms |
Novartis | February 2003 | Phase 3 |
| NCT00056446 | Completed | Drug: Vatalanib | Colorectal Neoplasms Colonic Neoplasms |
Novartis Pharmaceuticals | January 2003 | Phase 3 |
| NCT00134355 | Completed | Drug: PTK787 | Prostate Cancer | University of Michigan Rogel Cancer Center |
July 2005 | Phase 2 |
Effects of PTK787/ZK 222584 on the growth of a xenograft of the human epithelial carcinoma A431, implanted s.c. in BALB/c nude mice. Cancer Res. 2000 Apr 15;60(8):2178-89. |
Effects of PTK787/ZK 222584 on the tensile strength of an incisional wound in rats. Cancer Res. 2000 Apr 15;60(8):2178-89. |
Effect of PTK787/ZK 222584 treatment with and after cyclophosphamide on blood cells in normal BALB/c mice. Cancer Res. 2000 Apr 15;60(8):2178-89. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
